Conditions - UKMLA Flashcards
what is Addison’s disease?
Primary adrenal insufficiency
Give a description of adrenal insufficiency.
A failure of the adrenal gland to produce cortisol and aldosterone (mineralocorticoid)
Primary: due to destruction of the adrenal cortex
Secondary: Due to long-term exogenous steroid
Who is more affected (age and gender) by primary and secondary adrenal insufficiency?
Primary: 30-50 years, women more affected.
Secondary: 50-60 years, women more affected.
what are the risk factors of primary adrenal insufficiency (Addison’s disease)
Autoimmune destruction of the adrenal glands (Addison’s disease - adrenal auto antibodies)
Vitiligo, TB, HIV, Haemorrhage in the adrenal glands
Hormonal deficiency: congenital adrenal hyperplasia due to 21-hydroxylase, or less common 11-hydroxylase deficiency
what are risk factors of secondary adrenal insufficiency?
Most commonly due to exogenous steroid use
Also due to Adrenocorticotrophic (ACTH) deficiency, most commonly caused by a pituitary lesion.
Withdrawl of long standing steroid therapy.
what is the pathophysiology of primary adrenal insufficiency?
Due to autoimune destruction of the adrenal glands resulting in failure to secrete mineralocorticoids.
Aldosterone, which is the most crucial mineralocorticoid hormone, binds to mineralocortiocoid receptors in the kidney
This causes sodium retention and increased excretion of potassium
what is the pathophysiology of secondary adrenal insufficiency?
Long term steroid therapy leads to suppression of the pituitary-adrenal axis which is apparent on withdrawal of steroids.
The exogenous steroids increase cortisol level in the blood which is sensed by the hypothalamus, negative feedback regulation of the pituitary adrenal axis which will cause the hypothalamus to reduce the secretion of ACTH to thr adrenal causing a lack of stimulation.
what are the signs and symptoms of adrenal insufficiency?
Weight loss
Abdominal pain
Psychosis
Loss of pubic hair in women
Postural hypotension
Auricular cartilage calcification
Increased pigmentation
Addison’s - hyperpigmentation of the gums
High ACTH - pigmented palmar creases, buccal mucosa
what are signs of adrenal crisis (shock)?
Hypotension
tachycardia
Hyperthermia
Coma
what is the non-pharmacological management of adrenal insufficiency?
All patients with hypoadrenalism are advised to wear and/or carry a medic alert bracelet with them at all times
what is the pharmacological management of adrenal insufficiency?
Steroid replacement with glucocorticoids
Oral hydrocortisone and mineralocorticoids (fludrocortisone)
– Usual does should be doubled during stress or illness (sick day rule)
Significant postural hypotension can be corrected with fludrocortisone
what is the treatment for adrenal crisis (shock)?
Urgent treatment is necessary
IV bolus fluids
Electrolyte replacement - watch for high potassium, check ECG and give calcium gluconate if needed
IV steroid replacement (Hydrocortisone)
what are differential diagnosis for adrenal insufficiency?
Secondary hypodrenalism
Addison’s disease
Adrenal crisis
Symptomatic anaemia
Thyroid disorder
Malignancy
Autoimmune disorder: polymyalgia rheumatica, rheumatoid arthritis
what investigations should be carried out for addison’s disease?
1st investigations to order
Morning serum cortisol (<140nanomols/L)
Plasma ACTH with cortisol (>12picomols/L)
Serum electrolytes (low sodium, high potassium, high calcium)
Urea and creatinine (may be elevated)
FBC (Anaemia , eosinophillia, relative lymphocytosis and neutropenia)
Investigations to consider
Synacthen test (serum cortisol <500nanomols/L)
Plasma renin (low aldosterone/high renin)
Serum aldosterone (suppressed)
Adrenal antibodies (present)
Adrenal Ct or MRI
TSH (raised)
Synacthen test (ACTH levels high in Addison’s) (ACTH low in secondary adrenal insufficiency)
Autoantibodies - Addison’s
Diagnostic criteria: Addison’s vs secondary adrenal insufficiency?
Addison’s: ACTH high >500pg/ml, renin high and aldosterone low, autoantibodies
Secondary: ACTH low <5, RAAS can function normally
what is the prognosis of adrenal insufficiency?
Untreated hypoadrenalism and adrenal crisis is inevitable fatal.
Treatment for Addison’s disease is life long
Steroid replacement therapy should bring resolution of symptoms, but increased risk of cardiovascular disease, cancer and infection.
Explain the Adrenocorticotrophic hormone stimulation (synacthen) test.
For ACTH test in secondary care
Blood samples are obtained to check serum cortisol levels before and 30 minutes after administering 250micrograms tetracosactide (ACTH synthetic) IV or IM
A normal response to the ACTH stimulation test is an increase in serum cortisol levels
Normal: cortisol levels increase to more than 500-550 nanomol/L after 30-60 minutes
Adrenal insufficiency: serum cortisol levels do not increase sufficienctly in response to ACTH because the adrenal cortex is already receiving max stimulation from endogenous ACTH
what are investigations into adrenal suppression?
First:
Serum comprehensive chemistry panel (hypo/hyper glycaemia, hypokalemia, contraction alkalosis)
Serum a.m cortisol (<110 nanomol/L)
Salivary a.m cortisol (<414 nanomol/L)
ACTH stimulation test (serum cortisol >497 excludes adrenal insufficiency)
FBC (elevated WBC)
Thyroid function test (elevated free thyroxine)
Invetsigations to consider
Insulin tolerance test (serum cortisol <497)
Overnight metyrapone test (
urine synthetic glucocorticoids (may be positive)
what are other names for hyperaldosteronism?
Conn Syndrome
Mineralcortiocoid excess
Give a description of hyperaldosteronism (Conn)?
Primary hyperaldosteronism is the excessive production of aldosterone.
Hypokalemia and hypertension.
Sodium mildly raised/normal
what are causes of hyperaldosteronism?
Conn syndrome (2/3) - solitary aldosteroe-producing adenoma
Adrenocortical hyperplasia
what are risk factors for secondary hyperaldosteronism?
Due to reduced renal perfusion
- Renal artery stenosis
Accelerated hypertension
Diuretics use
Congestive cardiac failure
what is the pathophysiology of hyperaldosteronism?
Excess production of aldosterone that is not dependent on the RAAS causes more sodium and water retention with reduced renin release
what are signs/symptoms of hyperaldosteronism?
Hyperaldosteronism is often aymptomatic
Signs of hypokalemia:
- Weakness
- Cramps
- Paraesthesia
- Polyuria
- Polydypsia
- Hypertension
- Peripheral oedema
what are the investigations for hyperaldosteronism?
U&E
- Hypokalemia
- Sodium mildy raised/normal
Aldosterone renin ratio
- A high ratio = primary
- A low ratio = secondary
CT/MRI
- After hyperaldosteronism has been proven.
what is the diagnostic criteria for hyperaldosteronism?
Serum aldosterone - >20 ng/dL
Aldosterone renin ration of more than 20:1
what is the management for Adrenocorticol hyperplasia?
Spironolactone or amiloride
Eplerenone is selective aldosterone antagonist that can be used in patients who develop gynaecomastia or breast soreness with spironolactone
what is the management for GRA?
Dexamethasone 1mg/24 hours orally for 4 weeks would normalise biochemistry but not BP
what is the prognosis of hyperaldosteronism?
Treated has good prognosis
May need lifelong antihypertensives to control blood pressure.
what are differential diagnosis for hyperaldosteronism?
primary hyperaldosteronism (Conn, GRA, bilateral adrenocortical hyperplsia)
Seondary hyperaldosteronism
Renal artery stenosi s
Contraction of aorta
Diuretic use
Congestive heart failure
hepatic failure
